CIRS is a form of Systemic Inflammatory Response Syndrome (SIRS) and is characterized by (1) lack of regulation of host inflammatory response as evidenced by deficiency of alpha melanocyte stimulating hormone (MSH) and/or vasoactive intestinal polypeptide (VIP); (2) presence of more than one of Th1 responses (pro-inflammatory); Th2 responses (anti-inflammatory); Th17 responses (tied to transforming growth factor beta-1 (TGF-β1)); coagulation abnormalities, especially abnormalities in von Willebrand's profile; activation of complement split products; activation of elements under regulation of hypoxia inducible factor including vascular endothelial growth factor (VEGF) and erythropoietin; abnormal regulation of ACTH responses to cortisol and ADH responses to osmolality. CIRS may be acquired through different mechanisms, for example, an exposure to toxins or inflammagens that may include, but are not limited to, environmental biotoxins, and chronic illness from Lyme disease present even after treatment with antibiotics. The exposure to environmental sources of biotoxins includes a chronic exposure to the interior environment of water-damaged buildings (WDB), or ingestion of fish contaminated with the toxins of marine dinoflagellates, such as ciguatoxins. Other environmental sources of biotoxins that can lead to CIRS include certain compounds made by dinoflagellates, cyanobacteria, fungi, actinomycetes, bacteria, mycobacteria, etc. When CIRS is acquired because of an exposure to a WDB, it is termed CIRS-WDB (Expert Treating Physicians Consensus, 2010).
According to a report released by the World Health Organization in 2009, in a WDB, people are chronically exposed to different microbes and/or compounds of microbial or other origin that are present in the indoor air of a WDB. These compounds initiate an innate immune inflammatory response in the human host. These microbes and compounds include but are not limited to fungi, bacteria, actinomycetes, and mycobacteria and their toxins; as well as inflammagens from fragments of fungal structures; and beta glucans, mannans, hemolysins, proteinases, spirocyclic drimanes and volatile organic compounds (VOCs). An ongoing exposure to the above microbes and/or compounds can result in a recurrent activation of immune responses, leading to exaggerated immune responses and prolonged production of inflammatory mediators, especially in the absence of regulation of inflammation by neuropeptides MSH or VIP.
Some of the organisms that make biotoxins that can cause CIRS include dinoflagellates (Pfiesteria, Gambierdiscus (ciguatera), Karenia (and other species that produce brevetoxins) cyanobacteria (Microcystis, Cylindrospermopsis, Lyngbya wollei); fungi (Wallemia, Stachybotrys, Chaetomium, Trichoderma, Aspergillus versicolor, Aspergillus versicolor and others); actinomycetes (Streptomyces and others); apicomplexans (Babesia, Sarcocystis, Eimeria), and spirochetes (Borrelia spp burgdorferi and (likely) B. lonestari). Organisms such as commensal multiple-antibiotic resistant coagulase negative staphylococci (MARCoNS), including methicillin resistant Staphylococcus epidermidis, may also contribute to CIRS.
Two examples of inflammagens that may cause CIRS are beta-glucans and mannans made by fungi that activate specific C-type lectin receptors, namely dectin-1 and dectin-2 receptors.
Patients with CIRS are often misdiagnosed as having depression, stress, allergy, fibromyalgia, post traumatic stress disorder, Chronic Fatigue Syndrome or somatization, etc., and are treated with various therapies, some of them being potentially toxic, which have not yet been shown to be effective, and are often costly. One reason that CIRS may be misdiagnosed is because there are no biomarkers that have been identified yet for CIRS or for those commonly-misdiagnosed illnesses, which would allow for a confirmatory diagnosis. Treating CIRS patients for the above conditions does not improve their symptoms of CIRS. With proper detection, diagnosis, and documentation of the objective basis of illness pathophysiology, CIRS may be treated effectively to improve symptoms and decrease the recurrence of uncontrolled inflammatory responses. Therefore, there exists a need for accurate diagnosing of CIRS in order to effectively treat patients with CIRS.